The role of a low protein diet supplemented with ketoanalogues on kidney progression in pre-dialysis chronic kidney disease patients

In slowing kidney progression, numerous pre-dialysis chronic kidney disease (CKD) patients could not adhere to the well-established dietary pattern, including a very low protein diet, 0.3–0.4 g/kg/day, plus a full dose ketoanalogues (KAs) of amino acids. We evaluated the role of a low protein diet (LPD), 0.6–0.8 g/kg/day, combined with KAs (LPD–KAs) on CKD progression. We extracted data in the retrospective cohort using electronic medical records (n = 38,005). Participants with LPD–KAs for longer than six months were identified. An unmatched control group, LPD alone, was retrieved from the same database. Cox proportional hazard models were performed to examine the associations between LPD–KAs and outcomes. The primary outcome was either a rapid estimated glomerular filtration rate (eGFR) decline > 5 mL/min/1.73m(2)/year or commencing dialysis. Other secondary outcomes include changes in proteinuria, serum albumin, and other metabolic profiles were also assessed. A total of 1042 patients were finally recruited (LPD–KAs = 543). Although patients with LPD–KAs had significantly lower eGFR and a prevalence of diabetes, age, and dietary protein intake were comparable between LPD–KAs (0.7 ± 0.2 g/kg/day) and LPD alone groups (0.7 ± 0.3 g/kg/day, p = 0.49). During a median follow-up of 32.9 months, patients treated with LPD–KAs had a significantly lower risk of kidney function decline (HR 0.13; 95% CI 0.09–0.19, p < 0.001) and dialysis initiation (HR 0.24; 95% CI 0.12–0.49, p < 0.001) than LPD alone after adjusting for confounders. The annual rate of eGFR decline in patients receiving LPD–KAs was 4.5 [3.4–5.5] mL/min/1.73m(2) compared with 7.7 [6.0–9.4] mL/min/1.73m(2) in LPD alone (p = 0.001). According to KAs dose–response analysis, the daily dose of ≤ 5 tablets was conversely associated with a higher risk of the primary endpoint, whereas the association disappeared among patients receiving a dose of > 6 tablets. The spot urine protein creatinine ratio and serum phosphate levels were not significantly different between groups. LPD–KAs could retard kidney progression compared with LPD alone. This favorable effect was significant among CKD patients receiving a daily KAs dose of more than six tablets. Future randomized controlled trials should be performed to verify these findings.